rs736781

Variant names:

• chr7-30464544-C-T
• rs736781
• NM_006092.4:c.-351-4503G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006092.4(NOD1):​c.-351-4503G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,148 control chromosomes in the GnomAD database, including 3,843 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (3843 hom., cov: 33)
• Consequence: NOD1 NM_006092.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980
• Publications: 10 publications found

Genes affected

NOD1 (HGNC:16390): (nucleotide binding oligomerization domain containing 1) This gene encodes a member of the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family of proteins. The encoded protein plays a role in innate immunity by acting as a pattern-recognition receptor (PRR) that binds bacterial peptidoglycans and initiates inflammation. This protein has also been implicated in the immune response to viral and parasitic infection. Major structural features of this protein include an N-terminal caspase recruitment domain (CARD), a centrally located nucleotide-binding domain (NBD), and 10 tandem leucine-rich repeats (LRRs) in its C terminus. The CARD is involved in apoptotic signaling, LRRs participate in protein-protein interactions, and mutations in the NBD may affect the process of oligomerization and subsequent function of the LRR domain. Mutations in this gene are associated with asthma, inflammatory bowel disease, Behcet disease and sarcoidosis in human patients. [provided by RefSeq, Aug 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOD1	NM_006092.4	c.-351-4503G>A		intron_variant	Intron 1 of 13	ENST00000222823.9	NP_006083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOD1	ENST00000222823.9	c.-351-4503G>A		intron_variant	Intron 1 of 13	1	NM_006092.4	ENSP00000222823.4

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33101 AN: 152030 Hom.: 3836 Cov.: 33

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.252

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.218 AC: 33131 AN: 152148 Hom.: 3843 Cov.: 33 AF XY: 0.219 AC XY: 16275 AN XY: 74364

African (AFR) AF: 0.272 AC: 11262 AN: 41478

American (AMR) AF: 0.162 AC: 2475 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 687 AN: 3472

East Asian (EAS) AF: 0.365 AC: 1887 AN: 5172

South Asian (SAS) AF: 0.292 AC: 1408 AN: 4820

European-Finnish (FIN) AF: 0.175 AC: 1848 AN: 10590

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12900 AN: 68002

Other (OTH) AF: 0.252 AC: 534 AN: 2116

Alfa AF: 0.197 Hom.: 1069

Bravo AF: 0.221

Asia WGS AF: 0.333 AC: 1155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.7
DANN	Benign	0.57
PhyloP100		0.098
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs736781; hg19: chr7-30504160;